Coordinated responses of natural anticoagulants to allogeneic stem cell transplantation and acute GVHD – A longitudinal study
(2017) In PLoS ONE 12(12).- Abstract
Background Allogeneic stem cell transplantation (SCT) enhances coagulation via endothelial perturbation and inflammation. Role of natural anticoagulants in interactions between coagulation and inflammation as well as in acute graft-versus-host disease (GVHD) are not well known. The purpose of this study was to define changes in natural anticoagulants over time in association with GVHD. Patients and methods This prospective study included 30 patients who received grafts from siblings (n = 19) or unrelated donors (n = 11). Eight patients developed GVHD. Standard clinical assays were applied to measure natural anticoagulants, represented by protein C (PC), antithrombin (AT), protein S (PS), complex of activated PC with its inhibitor... (More)
Background Allogeneic stem cell transplantation (SCT) enhances coagulation via endothelial perturbation and inflammation. Role of natural anticoagulants in interactions between coagulation and inflammation as well as in acute graft-versus-host disease (GVHD) are not well known. The purpose of this study was to define changes in natural anticoagulants over time in association with GVHD. Patients and methods This prospective study included 30 patients who received grafts from siblings (n = 19) or unrelated donors (n = 11). Eight patients developed GVHD. Standard clinical assays were applied to measure natural anticoagulants, represented by protein C (PC), antithrombin (AT), protein S (PS), complex of activated PC with its inhibitor (APC-PCI) and by markers of endothelial activation: Factor VIII coagulant activity (FVIII:C) and soluble thrombomodulin (s-TM) at 6–8 time points over three months. Results Overall, PC, AT and FVIII:C increased in parallel after engraftment. Significant correlations between PC and FVIII:C (r = 0.64–0.82, p<0.001) and between PC and AT (r = 0.62–0.81, p<0.05) were observed at each time point. Patients with GVHD had 21% lower PC during conditioning therapy and 55% lower APC-PCI early after transplantation, as well as 37% higher values of s-TM after engraftment. The GVHD group had also increases of PC (24%), FVIII: C (28%) and AT (16%) three months after transplantation. Conclusion The coordinated activation of natural anticoagulants in our longitudinal study indicates the sustained ability of adaptation to endothelial and inflammatory activation during allogenic SCT treatment. The suboptimal control of coagulation by natural anticoagulants at early stage of SCT may contribute to onset of GVHD.
(Less)
- author
- Przybyla, Beata ; Pinomäki, Anne ; Petäjä, Jari ; Joutsi-Korhonen, Lotta ; Strandberg, Karin LU ; Hillarp, Andreas LU ; Öhlin, Ann Kristin LU ; Ruutu, Tapani ; Volin, Liisa and Lassila, Riitta
- organization
- publishing date
- 2017-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 12
- issue
- 12
- article number
- e0190007
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- scopus:85039167620
- pmid:29272282
- wos:000418651500023
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0190007
- language
- English
- LU publication?
- yes
- id
- 92b8a99c-7942-4b68-8022-52093ed35ca6
- date added to LUP
- 2018-01-08 10:27:43
- date last changed
- 2024-05-27 03:57:53
@article{92b8a99c-7942-4b68-8022-52093ed35ca6,
abstract = {{<p>Background Allogeneic stem cell transplantation (SCT) enhances coagulation via endothelial perturbation and inflammation. Role of natural anticoagulants in interactions between coagulation and inflammation as well as in acute graft-versus-host disease (GVHD) are not well known. The purpose of this study was to define changes in natural anticoagulants over time in association with GVHD. Patients and methods This prospective study included 30 patients who received grafts from siblings (n = 19) or unrelated donors (n = 11). Eight patients developed GVHD. Standard clinical assays were applied to measure natural anticoagulants, represented by protein C (PC), antithrombin (AT), protein S (PS), complex of activated PC with its inhibitor (APC-PCI) and by markers of endothelial activation: Factor VIII coagulant activity (FVIII:C) and soluble thrombomodulin (s-TM) at 6–8 time points over three months. Results Overall, PC, AT and FVIII:C increased in parallel after engraftment. Significant correlations between PC and FVIII:C (r = 0.64–0.82, p<0.001) and between PC and AT (r = 0.62–0.81, p<0.05) were observed at each time point. Patients with GVHD had 21% lower PC during conditioning therapy and 55% lower APC-PCI early after transplantation, as well as 37% higher values of s-TM after engraftment. The GVHD group had also increases of PC (24%), FVIII: C (28%) and AT (16%) three months after transplantation. Conclusion The coordinated activation of natural anticoagulants in our longitudinal study indicates the sustained ability of adaptation to endothelial and inflammatory activation during allogenic SCT treatment. The suboptimal control of coagulation by natural anticoagulants at early stage of SCT may contribute to onset of GVHD.</p>}},
author = {{Przybyla, Beata and Pinomäki, Anne and Petäjä, Jari and Joutsi-Korhonen, Lotta and Strandberg, Karin and Hillarp, Andreas and Öhlin, Ann Kristin and Ruutu, Tapani and Volin, Liisa and Lassila, Riitta}},
issn = {{1932-6203}},
language = {{eng}},
month = {{12}},
number = {{12}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Coordinated responses of natural anticoagulants to allogeneic stem cell transplantation and acute GVHD – A longitudinal study}},
url = {{http://dx.doi.org/10.1371/journal.pone.0190007}},
doi = {{10.1371/journal.pone.0190007}},
volume = {{12}},
year = {{2017}},
}